The present invention relates to novel antibacterial agents with multiple pharmacological action and to their process of preparation.
Research for antibacterial agents has led to the discovery of a wide variety of structures related to 1,4-dihydro 1-alkyl 4-oxo pyridine 3-carboxylic acids.
Thus, DAINIPPON pharmaceutical in British Pat. No. 1,129,358 (1966) describes the interesting antibacterial properties of derivatives of the general formula: ##STR2## comprising among others PIROMIDIC acid when R.sub.1 =pyrrolidine.
The same applicant describes, in its French Pat. No. 2,103,618 (1971) much superior antibacterial properties when the previously mentioned pyrrolidine ring is substituted. From the same basic structure, DAINIPPON claims in its French Pat. No. 2,196,159 (1973) the general structure: ##STR3## whose bactericidal activities are more interesting than those of the previously described homologs. Somewhat later, R. BELLON in his French Pat. No. 2,364,920 (1977) claims derivatives according to the above general formula giving the radical R.sub.1, meanings not previously claimed, namely carbonyl radicals, whereas at the same time DAINIPPON in its French Pat. No. 2,359,140 (1977) claimed this same general formula but where R.sub.1 =NH.sub.2 --phenyl--CH.sub.2 -- resulting in an antibacterial activity which was quite satisfactory both in vitro and in vivo against gram positive and gram negative bacteria.
In this same series of 1-alkyl 4-pyridone 3-carboxylic acids, NALIDIXIC acid was the subject of French application No. 1,427,608 (1962) of STERLING DRUG according to the general formula: ##STR4## where X represents a carboxy, carbalkoxy, or carbamyl group.
From this structure, YAMANOUCHI formed the amide of ampicillin (B. Fr. 2,183,895) and FUJIMOTO that of cephalexine (B. Jap. 82.46990).
This general structure is defined by R. BELLON B. Fr. No. 2,500,833 who claims the derivatives of the general formula: ##STR5## for its bactericidal activities particularly with respect to grams.
The series of 1,4 dihydro 1-ethyl 4-oxo pyridine carboxylic acids determines with a condensed aromatic ring a quinolone of which oxolinic acid: ##STR6## represents the head of the series (B. Fr. M 4148 WARNER LAMBERT). This 3 carboxylic quinolone structure was gradually refined to arrive at PERFLOXACINE. ##STR7## of Roger BELLON, or at ROSOXACINE of STERLING DRUG (U.S. Pat. No. 3.753.993), ##STR8## or again NORFLOXACINE (U.S. Pat. No. 4,292,317). ##STR9## It is seen that therefore in the course of time structures have been evolved with the same basic structure and whose pharmacological properties particularly antibacterial are increasing.
The derivatives of oxolinic or nalidixic acid, ENOXACINE, PERFLOXACINE, NORFLOXACINE, ROSOXACINE or the derivatives of pipemidic acid are very valued and widely used antibacterial agents.